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Enrolling by invitationNCT04031508CDH-PPHN-N3Updated Mar 18, 2026

Effect of a Parenteral Emulsion With Omega3 on Neonates With PPHN and CDH

A Phase 2 interventional study of lipid injectable emulsion with Fish oil in Pulmonary Hypertension of Newborn and Diaphragm Defect, sponsored by Coordinación de Investigación en Salud, Mexico. Enrolling by invitation at 1 site in Mexico. Open to participants aged 1 Hour to 15 Days. Per ClinicalTrials.gov, last updated 2026-03-18.

Sponsored by Coordinación de Investigación en Salud, Mexico · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
1 Hour to 15 Days
Sex
All
01

Study summary

The purpose of this study is to evaluate the effect of a parenteral emulsion containing n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in fish oil on clinical outcomes, markers of inflammation and oxidative stress, and pain in neonates with persistent pulmonary hypertension of the newborn (PPHN) compared with those who receive an emulsion containing soy oil and medium-chain triglycerides (MCT) without n-3 LC-PUFA.

Read the detailed description

Background. Persistent pulmonary hypertension of the newborn (PPHN), is a syndrome characterized by difficulty to provide normal pulmonary vasodilatation at birth or after birth, which may be related to right ventricular dysfunction, congenital diaphragmatic hernia, sepsis, and meconium aspiration. This condition is understudied. PPHN causes pulmonary vascular resistance (PVR) that decreases left pulmonary artery flow (LPA), meaning that blood cannot be oxygenated in the lungs, leading to low oxygen delivery to all organs. Expensive medication along with ventilator support may help, but the latter and PPHN increase the production of the inflammatory mediators such as pro-inflammatory cytokines and markers of oxidative stress, which cause cell toxicity. To treat the hernia, infants undergo corrective surgery, which further increases the production of inflammatory markers and worsens oxidative stress. As a result, the pain of the surgery also worsens the hypoxemia and respiratory insufficiency in the newborn. PPHN is associated with chronic lung disease (CLD). To date, there is no effective treatment for neonates with PPHN, and around one-third of patients may not respond to current management, leading to the death of up to 33% of infants in developed countries. In Mexico, the mortality rate from PPHN may reach 80%, which is an unacceptable outcome at a high cost. Therefore, the prevention or reduction of the severity of PPHN is actively sought.

Previous reports have shown that the n-3 long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA) improves the nutritional status and clinical outcomes in septic newborn reduce systemic inflammation and organ dysfunction in newborns who underwent cardiovascular surgery with a shorter stay in the neonatal intensive care unit. In addition, those babies received lower amounts of analgesics. Other authors have shown that n-3 LC-PUFA reduces oxidative stress. In experimental models of PPHN, the EPA and DHA from Omegaven (fish oil) increased pulmonary artery flow and decrease pulmonary vascular resistance. In the current project, it is hypothesized that n-3 LC-PUFA improves clinical outcomes such as decreasing pulmonary vascular pressure and markers of inflammation and oxidative stress in neonates with PPHN. This hypothesis has not been evaluated.

Objective. The purpose of this study is to evaluate the effect of a parenteral emulsion containing n-3 LC-PUFA in fish oil on clinical outcomes, markers of inflammation and oxidative stress, and pain in neonates with PPHN compared with those who receive an emulsion containing soy and medium-chain triglycerides (MCT) without n-3 LC-PUFA.

Methodology. A double-blind clinical trial will be carried out on Mexican newborns diagnosed with PPHN. The control group will receive intravenous nutrition support including a lipid emulsion based on soy oil plus MCT (control group) and the intervention group will receive a lipid emulsion based on soy oil, MCT, olive oil, and fish oil (n-3 LC-PUFA group); both groups will receive a dose of lipid (3 g/kg/d maximum), through total parenteral nutrition (TPN) for at least 7 days.

The effect of n-3 LC-PUFA will be evaluated on:

  1. Clinical outcomes, nutritional status, the manifestation of pain
  2. Markers of inflammation
  3. Oxidative stress markers

To compare the groups, the Exact Fisher´s, Student's t, or U-Mann-Whitney tests will be applied as appropriate. To adjust the effect of n-3 LC-PUFA for confounders such as fatty acid background and medication, Repeated Measures ANOVA and binary logistic regression will be performed.

02

Conditions studied

  • Pulmonary Hypertension of Newborn
  • Diaphragm Defect

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Keywords

  • PPHN
  • Diaphragmatic Hernia
  • omega 3
  • DHA and EPA
03

Who can participate

Ages eligible
1 Hour to 15 Days
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Plan to administrate TPN for at least 7 days
  • Clinical, gasometric, and echocardiographic diagnosis of congenital diaphragmatic hernia.
  • Gestational age >=34 weeks.
  • Written informed consent signed by both parents after an explanation of the objectives, procedures and possible risks and benefits of the research, along with the signature of two witnesses

Exclusion criteria

Exclusion Criteria:

  • Diagnosis of complex congenital cardiopathy
  • Cyanotic congenital cardiology defect
  • Insufficiency of the tricuspid valve
  • Immunosuppressive disease. HIV has been associated with PPHN and human herpesvirus with vascular remodeling, perivascular macrophages, and lung fibrosis
  • Clinical entities that preclude the total parenteral nutrition for one day or longer.
  • Presence of profuse and persistent haemorrhage at any level

Elimination criteria

  • Parents who withdraw their consent.
  • Starting a drug at doses for nonclotting treatment such as heparin, enoxaparin.
  • Development of profuse and persistent haemorrhage at any level after receiving vitamin K treatment.
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
40 participants (estimated)

Study arms

  • Experimental
    Omega 3

    The experimental group will receive a parenteral emulsion containing soy oil, MCT, olive oil and n-3 LCPUFA in fish oil

    Combination Product: lipid injectable emulsion with Fish oil

  • Sham comparator
    Control group

    The Control group will receive a parenteral emulsion containing soy oil and MCT

    Combination Product: lipid injectable emulsion with Fish oil

Interventions

  • Combination productlipid injectable emulsion with Fish oil

    TPN will start at 1.5-2.0 g/kg/d of the lipid emulsion, increasing 1.0 g/kg/d until a maximum of 3.0 g/kg/d for at least 7 days.

    Also known as: SMOFLIPID

05

What researchers measure

Primary outcomes

  1. Change on systolic pressure of pulmonary artery

    Measured by echocardiography in millimeters of mercury (mm/Hg)

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.

  2. Preductal partial pressure of carbon (PaCO2)

    Good response if the carbon in blood is \<60-70 mmHg measured by gasometry in arterial blood

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour and day 7 post-surgery.

  3. Change in Preductal and postductal oxygen saturation (SatO2)

    It is a measure of oxygenation in hemoglobin. It is preductal if the measurement id on hand, and postductal if it is on foot, determined by an pulse oximeter in percentage

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.

  4. Inspired fraction of oxygen (FiO2)

    Oxygen concentration supplied by ventilation support in percentage

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.

  5. Growth velocity and Nutritional status

    Measurement of body weight in grams, length, and head circumference in centimeters (if clinical condition allows it) to obtain grams/kg/d, cm/week, Z score, and eutrophic or undernutrition outcome using the Fenton's standard reference of growth and/or World Health Organization as appropriate for preterm or term infants, respectively.

    Time frame: Before surgery (baseline), day 7, day 14 and day 21 post-surgery.

  6. Pain manifestation

    Pain will be measured with the COMFORT scale computed by eight sections with scores from 1 to 5 each.

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.

Secondary outcomes

  1. Concentration of plasma cytokines as inflammatory markers

    Determination of pro and anti-inflammatory cytokines interleukin (IL)-1beta, tumoral necrosis factor-alpha, IL-6, IL-8, IL-10, IL-12 (p70) (pg/milliliter) in plasma by luminex-based immunoassay.

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, and day 7 post-surgery.

  2. Concentration of inflammatory derived-lipid mediators

    Determination lipid mediators such as eicosanoids and resolvin(s) in ng/ml by liquid chromatography coupled to mass spectrometry.

    Time frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, and day 7 post-surgery.

  3. Concentration of total free thiols

    This will be measured in urine by ELISA in pg/milliliter

    Time frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.

  4. Concentration of nitrotyrosine

    This will be measured in urine by ELISA in micromol per liter (uM)

    Time frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.

  5. Concentration of the nuclear factor erythroid 2-related factor 2 (Nrf2)

    This will be measured in urine by ELISA in pg/milliliter

    Time frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.

  6. Concentration of Ratio of F2-isoprostanes (F2-isop) and F2-isofurans (F2-isof)

    This ratio will be measured in urine in nmol/liter by Liquid chromatography coupled to mass spectrometry.

    Time frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.

  7. Chronic Lung Disease

    It will be evaluated with the need of supplementary Oxygen and/or medication to improve lung function

    Time frame: At hospital discharge or 56 day-old, at 6 months and one year of age

06

Study locations

1 site
  • Unit of Medical Research in Nutrition
    Mexico City, Mexico City 06720, Mexico
07

References and documents

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04031508
Lead sponsor
Coordinación de Investigación en Salud, Mexico
Collaborators
University of Southampton, Universidad Nacional Autonoma de Mexico
Responsible party
Mariela Bernabe García (Full time researcher, Coordinación de Investigación en Salud, Mexico) — Principal investigator
First posted
Jul 24, 2019
Start date
Aug 12, 2019
Primary completion
Nov 2026 (estimated)
Completion
Dec 2026 (estimated)
Last update
Mar 18, 2026

Study contacts

Mariela Bernabe-Garcia, Ph.D.
principal investigator · Instituto Mexicano del Seguro Social

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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